The Uniocular Drug Trial and Second-Eye Response to
Glaucoma
Medications
Tony Realini, MD, Robert D. Fechtner, MD, Sean-Paul Atreides,
MD, Stephen Gollance, MD
Ophthalmology, March 2004
Results: Intraocular pressure dropped a mean of 5.7 +/- 3.8
mmHg (mean +/- standard deviation) in the first eye after a
uniocular trial, and 2.8 +/- 3.3 mmHg in the second eye after
bilateral use. Regression analysis demonstrated a poor correlation
between first-eye and second-eye response to the same medication.
To minimize possible contralateral IOP effects of first-eye
therapy, a subset of 26 patients treated with latanoprost (which
has little if any contralateral IOP effect, due to rapid systemic
metabolism) was studied, with no improvement in correlation.
Conclusion: Uniocular trials of glaucoma medications do not
adequately predict second-eye IOP responses to the same medications.
If both eyes of a glaucoma patient require IOP reduction, one
should not assume that magnitudes of response will be equal
in both eyes. The effect of a given medicine must be assessed
independently for each eye.
Select Quotes
"We are not confident that fellow eyes can serve as each
others' controls. This is not to say that IOP is not similar
in fellow-eye pairs. Indeed, very likely it is - on average.
Over time, the average IOP is likely to be very similar in
fellow-eye pairs. But to believe that the IOP in fellow eyes
is identical or nearly so at every instant is not supported
and, in fact, is disproved by the existing literature."
"Our data show surprisingly but convincingly that the
uniocular drug trial does not predict second-eye IOP reductions
after treatment with the same medication."
"This retrospective study is subject to all the limitations
and artifacts known to affect such endeavors. Despite the
limitations, our findings are not merely of marginal statistical
significance. No matter how we attempted to clean the data
to minimize artifacts, there simply was no correlation to be
found between the uniocular trial results and the second-eye
IOP response."
"We are underway with additional studies to further elucidate
these preliminary findings, and we suggest 2 consequences of
our current findings. The first is that the uniocular trial
is likely to be unhelpful and unnecessary in glaucoma management.
The purpose of the uniocular trial is to determine if a given
drug works for a given patient. This is based on the assumption
that fluctuation in IOP tends to be similar in both eyes. This
is not true. We also have assumed that if one eye responds
well to a medication, the other will as well. Our data do not
support that assumption. Therefore, none of the assumptions
underlying the one-eye trial are supported by our retrospective
studies. Instead, we need a trial that determines if a given
drug works for a given eye, and the same test must be performed
on both eyes of a two-eyed patient. The simplest solution is
to begin treatment in both eyes simultaneously and assess each
eye separtely in terms of IOP response. We cannot generalize
the IOP response to treatment observed in one eye to the fellow
eye."
"Our preliminary data, reported here, suggest that fellow
eyes may well be independent in terms of therapeutic responses
to IOP-lowering medications, and the benefits of halving study
sample sizes may well outweigh the probably small risk of bias."
M&T Commentary: This retrospective study of 52 patients
at a university-based glaucoma speciality service flies in
the face of decades of conventional practice, and indeed many
doctor-years of glaucoma patient care. How could we have all
been so wrong all these years?
While we certainly understand - and appreciate - this new
revelation, our current practice patterns will not change.
Not that we are stubborn, however, we have successfully cared
for many hundreds of patients with glaucoma for nearly 50 years
between the two of us using the monocular therapeutic trial
as one of our foundations of medical therapy. Notwithstanding,
if a prospective study is conducted using a patient base more
like that seen in the general community, we wll have to take
a strong look at altering our modus operandi.
While these findings are of interest, and certainly thought
provoking, it must remember that "target pressure" is
currently our ultimate guide to drug efficiacy. So, while the
monocular trial provides general guidance regarding drug efficiacy,
our vigilence regarding achievement of a safe IOP remains our
ultimate safeguard of functional visual performance.
|
